P1596: EFFICACY AND SAFETY OF QL0911 IN ADULT PATIENTS WITH CHRONIC PRIMARY IMMUNE THROMBOCYTOPENIA: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III TRIAL
Authors: Hu Zhou, Ming Hou, Yan Shi, Jie Jin
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: ITP-related national and international guidelines explicitly recommend TPO-RAs as a key option for second-line treatment. QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein for injection, is a biosimilar to romiplostim (Nplate®) developed by Qilu Pharmaceutical Co., Ltd., for the treatment of chronic ITP in adults and other indications. Preclinical studies of QL0911 revealed that it was highly consistent with licensed romiplostim in terms of structure, physicochemical properties, biological activity, and pharmacokinetics (PK), and it was well tolerated without severe drug-related toxicity (data submitted for publication). Aims: Therefore, we conducted this phase III study, aiming to demonstrate the superiority of QL0911 to placebo in raising and maintaining platelet counts in patients with chronic ITP within a target range (≥50×109/L) over a 24-week treatment period and to evaluate the efficacy and safety of long-term treatment over 42 weeks. Methods: We conducted a double-blind, placebo-controlled, phase III study in patients with diagnosed primary ITP for at least 12 months, who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who had relapsed after splenectomy from 44 sites in China. Patients were randomly allocated (in a 2:1 ratio) treatment with QL0911 or placebo injected subcutaneously once weekly at an initial dose of 1 μg/kg for 24 weeks. Doses were adjusted to maintain target platelet counts of 50×109/L to 200×109/L. Patients and investigators were blinded to this assignment. The primary endpoint was the proportion of patients achieving durable platelet response at week 24 (a platelet count ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. This study is registered with ClinicalTrials.gov (NCT05621330). Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911: 144, placebo: 72). Durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% confidence interval [CI]: 53.3-69.8%; P＜0.0001) than in the placebo group. The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE: 0.26) weeks with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no) or concomitant ITP treatment (yes/no) or baseline platelet count (≤10×109/L, >10×109/L and ≤20×109/L, >20×109/L and <30×109/L). Incidences of TEAEs were comparable between QL0911 and placebo groups (91.7% versus 88.9%). The most common adverse events were upper tract respiratory tract infection (31.9% on QL0911 vs. 27.8% on placebo), urinary tract infection (19.4% vs. 12.5%), and arthralgia (13.2% vs. 6.9%). Summary/Conclusion: QL0911 was well tolerated, and increased and maintained platelet counts in adults with ITP. QL0911, as a biosimilar of romiplostim (Nplate®), may become a novel treatment option for ITP patients with failure or relapse from first-line treatment in China. Ongoing studies will provide further data as to long-term efficacy and safety in such patient populations.Keywords: Thrombopoietin (TPO), ITP